Regenerative dialysis systems, such as the Recirculating Dialysate System (“REDY” System) contain regenerative substances that remove impurities, waste products and certain electrolytes from spent dialysate to result in cleansed dialysate that can be reconstituted and reused. Depending on the dialysis treatment being performed, several kilograms of sorbent materials may be required for dialysate regeneration. Hence, there is a need for systems and methods that minimize the amount of sorbent material required during hemodialysis, hemofiltration, hemodiafiltration and peritoneal dialysis. There is also a need for systems and methods having decreased weight and cost of a regeneration module. There is further a need for configurations of regeneration modules such as sorbent cartridges that reduce the amount of regenerative substances that are consumed during dialysate regeneration.